Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inner cytosine methylation was analyzed in the CCWGG sequences of the 5'-terminal region of the human calcitonin gene from peripheral blood and bone marrow cells in various forms of leukemia. Since these sequences remain nonmethylated both in norm and in various leukemia forms, the CpG dinucleotide hypermethylation of the 5'-terminus of the human calcitonin gene, characteristic for the development of leukemias, does not spread over adjacent CpNpG sequences.
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PMID:[The lack of the CpNpG methylation at the 5'-terminal region of the human calcitonin gene in norm and in leukemia []. 1090 May 12

Germ line mutations of the RET proto-oncogene are responsible for the development of multiple endocrine neoplasia type 2A (MEN 2A), an inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. To study the mechanism of tissue-specific tumor development by RET with a MEN2A (cysteine 634-->arginine) mutation, we generated transgenic mice by introducing the RET-MEN2A gene fused to Moloney murine leukemia virus long terminal repeat. Expression of the transgene and its product was detected at variable levels in a variety of tissues including thyroid, heart, liver, colon, parotid gland, and brain. All of 29 mice analyzed developed thyroid C-cell hyperplasia or medullary carcinoma, accompanying high levels of serum calcitonin. In addition, development of mammary or parotid gland adenocarcinoma was observed in one-half of the transgenic mice. RET dimerization and its complex formation with Shc and Grb2 adaptor proteins were detected in tumor tissues. Unexpectedly, no tumor formation was found in other tissues despite RET-MEN2A expression where RET dimerization was undetectable. Because these tissues but not tumors expressed glial cell line-derived neurotrophic factor family receptor alpha (GFR alpha) at high levels, this suggested that GFR alpha expression may interfere in the dimerization of the RET-MEN2A mutant proteins, leading to tissue-specific tumor development in vivo.
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PMID:Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation. 1101 55

Classical and contemporary studies have shown that endocrine regulation exerted by ovarian hormones priming the endometrium is essential for embryo implantation. Increasing evidence indicates that steroid-induced molecules acting as paracrine modulators are necessary for embryo-uterine interactions. That is the case for calcitonin, heparin-binding epidermal growth factor (EGF)-like growth factor, leukaemia inhibitory factor and other molecules. Furthermore, when the blastocyst enters the uterine cavity, it starts the complex signals that will drive embryo adhesion. The paracrinology of this process is based on the local interplay of molecules, such as the secretion of cytokines that may facilitate the acquisition of endometrial receptivity by controlling the expression of adhesion and anti-adhesion proteins. Finally, during the embryonic invasive phase, uterine stromal-trophoblast dialogue may modulate this self-controlled proteolytic and immunological process to avoid damage to both the embryo and maternal environment.
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PMID:Paracrine regulators of implantation. 1102 2

We analysed calcitonin (CALC1) gene hypermethylation using semiquantitative differential polymerase chain reaction in 105 patients with adult (n = 49) and childhood (n = 56) acute lymphoblastic leukaemia (ALL), and studied the association of CALC1 hypermethylation with clinical presentation features and disease outcome. We also investigated the possible relationship between CALC1 methylation status and expression of the cell cycle inhibitor gene p57KIP2. We observed CALC1 hypermethylation in bone marrow cells from 43% (45 out of 105) of ALL patients. Clinical, molecular and laboratory features did not differ significantly between hypermethylated and hypomethylated patients, only T-cell lineage was associated with hypermethylation (14% vs. 47%, P = 0025). Complete remission rate was similar in both groups although hypermethylated patients had a higher relapse rate (68% vs. 19%, P < 0.00001) and mortality rate (55% vs. 36%, P = 0.06) than hypomethylated patients. Estimated disease-free survival (DFS) at 6 years was 66.1% for hypomethylated patients and 5.3% for hypermethylated patients (P < 0,00001). Multivariate analysis from potential prognostic factors demonstrated that CALC1 methylation status was an independent prognostic factor in predicting DFS (P = 0.0001). Separate analysis of adult and childhood ALL patients showed similar results to the whole series. In addition, hypermethylated patients showed downregulation of p57KIP2 expression. Our results suggest that CALC1 gene hypermethylation is associated with an enhanced risk of relapse independently of known poor-prognostic factors and we describe, for the first time, a possible implication of the p57KIP2 gene in the genesis and prognosis of ALL.
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PMID:Hypermethylation of the calcitonin gene in acute lymphoblastic leukaemia is associated with unfavourable clinical outcome. 1138 Mar 96

Methylation of the 5'-region of the calcitonin gene was investigated in bone marrow and peripheral blood cells of 27 healthy volunteers and 25 leukemic patients. In all patients suffering from various forms of myeloid and lymphoid leukemia, hypermethylation of CpG sequences was observed in this region of the calcitonin gene. Cytosine hypermethylation in the CpG sequence did not involve cytosines of adjacent CpNpG sequences (where N is any nucleoside). The 5'-region of the calcitonin gene lacked CpNpG methylation both in healthy controls and in leukemic patients; this apparently represents specific "non-alternative" type of CpG methylation in the extended DNA sequence. Methylation of the calcitonin gene was monitored in 18 leukemic patients during malignant progression and medical treatment. Hypermethylation of the calcitonin gene was not observed on long-term clinical hematological remission. In ten patients characterized by unstable (or incomplete) remission hypermethylation of the calcitonin gene persisted through the whole period of observation. In relapses, hypermethylation of the calcitonin gene appeared again and in six patients, this "molecular relapse" being registered 1-8 months before onset of clinical and laboratory signs of disease progression. The leukemia-specific hypermethylation of CpG sequences of the 5'-region of the calcitonin gene is a promising prognostic and diagnostic marker of leukemias and might be useful for monitoring of this disease.
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PMID:Hypermethylation of 5'-region of the human calcitonin gene in leukemias: structural features and diagnostic significance. 1506 3

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) belong to a calcitonin-family of regulatory peptides. Receptors for CGRP and ADM have been suggested to be present on both mucosal (MMC) and connective tissue (CTMC) type of mast cells, based on histamine release by these peptides. Recently, it was reported that mRNA for ADM receptors, but not for CGRP receptors, was expressed in rat peritoneal mast cells, a representative of type CTMC. However, mRNA expression for the receptors in MMC has not been studied yet. Therefore, we examined whether mRNAs encoding CGRP or ADM receptor subunit, RDC-1, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) are present, and if so, whether their expression is modified by IgE receptor triggering, in a mucosal type mast cell line, rat basophilic leukemia (RBL-2H3) cells using RT-PCR. RBL-2H3 cells constitutively express mRNA for RDC-1, CRLR, RAMP3 but not that for RAMP1 and RAMP2, and IgE receptor triggering was shown neither to induce the gene expression of RAMP1 and RAMP2, nor to enhance that of RDC-1, CRLR or RAMP3. These results indicate that RBL-2H3 cells posses receptors for both CGRP and ADM, suggesting various functions of these peptides in physiological and pathophysiological conditions where mast cells of the mucosal type are involved.
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PMID:The expression of mRNA for calcitonin gene-related peptide receptors in a mucosal type mast cell line, RBL-2H3. 1518 41

BACKGROUND Malignant hypercalcemia is a rare finding in the pediatric population, even more rare in hematological malignancies, such as leukemia. CASE REPORT We present a case of a 6-year-old female patient who was diagnosed with acute lymphoblastic leukemia, with secondary hypercalcemia. She started chemotherapy following the IC-BFM ALL2002 protocol with simultaneous calcitonin, diuretics and aggressive hydration for hypercalcemia, and went into complete remission after the induction therapy. After 4 months of chemotherapy, she was diagnosed with relapse associated again with malignant hypercalcemia, and underwent chemotherapy with the relapse protocol. There was no response after the first 2 cycles, so we decided to start her on clofarabine. Due to the severe hypercalcemia and consecutive osteolysis, she developed several bone fractures and needed gypsum immobilization. We started her again on calcitonin, but she developed severe adverse reactions, so we found it necessary to start bisphosphonates, first zoledronic acid intravenously, and afterwards clodronate orally. Consolidation of bone fractures was achieved, but due to prolonged immobilization she developed bedsores, superinfected with Lichtheimia corymbifera. We started posaconazole orally, but she rapidly went into severe sepsis with multiple organ failure. The leukemia showed no response to chemotherapy, progressed rapidly, and the patient died. CONCLUSIONS Malignant hypercalcemia is associated with a poor prognosis in leukemia, and might need a more aggressive therapy.
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PMID:Acute Lymphoblastic Leukemia with Malignant Hypercalcemia: A Case Report. 3091 42


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